Napsin A

Napsin A is an aspartic proteinase, and is normally found in lung pneumocytes and alveolar macrophages, pancreatic acini and ducts, and renal tubules.  Neoplastic tissue which stains with Napsin A includes:  lung adencarcinoma, renal cell carcinoma (clear cell and papillary), thyroid (papillary) carcinoma, and ovarian clear cell carcinoma.
 
Napsin A is primary used in combination with TTF-1 in identifying lung adencarcinomas (TTF-1 appears to be a little more sensitive in poorly differentiated tumors).  While approximately 97% of Napsin A expressing lung adenocarcinomas express TTF-1, up to 13% of TTF-1 negative cases express Napsin A.  The more recent description of Napkin A expression in 100% of ovarian clear cell carcinomas by Kandalaft, et al. further emphasizes the importance of using an appropriate panel of IHC stains for a given differential diagnosis to obtain optimal sensitivity and specificity.
 
In the setting of ovarian tumors (Kandalaft, et al.), Napsin A was 100% sensitive for ovarian clear cell carcinoma.  Endometrioid carcinomas of the ovary had focal Napsin A expression in 10% of cases, but no cases of high grade serous carcinoma or serous borderline tumor demonstrated expression.

Napsin A and TTF-1 expression in poorly differentiated non-small cell carcinomas (Mukjopadhyay, S, et al).
Tumor
Napsin A
TTF-1
Adenocarcinoma
11/19 (58%)
16/20 (80%)
Squamous Cell Carcinoma
0/15 (0%)
0/15 (0%)
Large Cell Carcinoma
0/4 (0%)
2/4 (50%)
 
Napsin A and TTF-1 expression in various tumor types (Bishop, JA, et al).
Tumor
Napsin A
(% positive)
TTF-1
(% positive)
Lung Tumors
 
 
Adneocarcinoma
79/95 (83%)
69/95 (73%)
–  Well-differentiated
42/47 (89%)
38/47 (81%)
–  Moderately-differentiated
27/32 (84%)
24/32 (75%)
–  Poorly-differentiated
11/16 (69%)
7/16 (44%)
Squamous Cell Carcinoma
0/46 (0%)
0/48 (0%)
Large Cell Carcinoma
3/9 (33%)
4/9 (44%)
Small Cell Carcinoma
0/3 (0%)
1/3 (33%)
Atypical Carcinoid Tumor
0/1 (0%)
1/1 (100%)
Typical Carcinoid Tumor
0/2 (0%)
1/2 (50%)
Nonpulmonary Adenocarcinomas
 
 
Colon Adenocarcinoma
0/5 (0%)
0/5 (0%)
Pancreas Adenocarcinoma
0/31 (0%)
0/31 (0%)
Breast Adenocarcinoma
0/17 (0%)
0/17 (0%)
Mesothelioma (all types)
0/38 (0%)
0/38 (0%)
Renal Cell Carcinomas
 
 
Clear Cell
14/41 (34%)
0/41 (0%)
Papillary
34/43 (79%)
0/43 (0%)
Chromophobe
1/34 (3%)
0/34 (0%)
Thyroid Lesions
 
 
Papillary Carcinoma
2/38 (5%)
37/38 (97%)
Follicular Carcinoma
0/15 (0%)
15/15 (100%)
Follicular Adenoma
0/28 (0%)
28/28 (100%)

 


Microscopic Images
Napsin A - Lung Adenocarcnioma
Napsin A – Lung Adenocarcinoma
Napsin A - Lung Squamous Cell Carcinoma
Napsin A expression in benign pneumocytes and histiocytes, and absence of staining in the squamous cell carcinoma (right side of image).
TTF-1/Napsin A (double stain) - Lung Adenocarcinoma
Napsin A (red) and TTF-1 (DAB) double stain in a lung adenocarcinoma. Note the granular staining characteristics of Napsin A.
Napsin A - Lung Squamous Cell Carcinoma
Napsin A expression in benign pneumocytes and histiocytes, and absence of staining in the squamous cell carcinoma (right side of image). Don’t mistake scattered intra-tumoral staining histiocytes as focal expression in the tumor.
TTF-1/Napsin A (double stain) - Lung Adenocarcinoma
Napsin A (red) and TTF-1 (DAB) double stain in a lung adenocarcinoma.
Napsin A - Lung Adenocarcnioma
Napsin A expression in lung adenocarcinoma. Note the granular characteristics of the cytoplasmic staining.

References
Eisen, RN, et al. Appl Immunohistochem Mol Morphol.  Vol. 19, No. 6, December 2011.
 
Bishop, J. A., Sharma, R., & Illei, P. B. (2010). Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma. Human Pathology, 41(1), 20–25. doi:10.1016/j.humpath.2009.06.014
 
Mukhopadhyay, S., & Katzenstein, A.-L. A. (2011). Subclassification of non-small cell lung carcinomas lacking morphologic differentiation on biopsy specimens: Utility of an immunohistochemical panel containing TTF-1, napsin A, p63, and CK5/6. The American Journal of Surgical Pathology, 35(1), 15–25. doi:10.1097/PAS.0b013e3182036d05   
 
Köbel M, Duggan MA. Napsin a: another milestone in the subclassification of ovarian carcinoma. Am J Clin Pathol. 2014;142(6):735–737. doi:10.1309/AJCPAVGZKA1A1HVC.
 
Kandalaft PL, Gown AM, Isacson C. The lung-restricted marker napsin a is highly expressed in clear cell carcinomas of the ovary. Am J Clin Pathol. 2014;142(6):830–836. doi:10.1309/AJCP8WO2EOIAHSOF.
 
Fadare O, Desouki MM, Gwin K, Hanley KZ, Jarboe EA, Liang SX, et al. Frequent Expression of Napsin A in Clear Cell Carcinoma of the Endometrium: Potential Diagnostic Utility. Am J Surg Pathol. 2013. doi:10.1097/PAS.0000000000000085